Practical Considerations for the Use of Sparsentan in the Treatment of Patients with IgAN in Clinical Practice

Abstract

Kirk N Campbell,1 Siân Griffin,2 Howard Trachtman,3 Rob Geletka,4 Muh Geot Wong5,6 1Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Department of Nephrology, University Hospital of Wales, Cardiff, UK; 3Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; 4Travere Therapeutics, Inc., San Diego, CA, USA; 5Department of Renal Medicine, Concord Repatriation General Hospital, Concord, NSW, Australia; 6Concord Clinical School, University of Sydney, Concord, NSW, AustraliaCorrespondence: Kirk N Campbell, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1243, New York, NY, 10029, USA, Tel [phone], Fax [phone], Email [email protected]: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is characterized by the mesangial deposition of IgA-containing immune complexes, triggering damage to the glomerular filtration barrier that is amplified by the tandem action of endothelin-1 and angiotensin II at their receptors. Proteinuria and progressive glomerular damage cause loss of kidney function in up to 50% of patients within 10– 20 years. The risk of progression is strongly associated with persistent proteinuria (> 0.75– 1 g/day). Current standard of care involves interventions to decrease proteinuria and control blood pressure. Immunosuppressive agents, used in selected patients at high risk for progression, can be associated with significant side effects. Sparsentan, a novel non-immunosuppressive single-molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA), received FDA accelerated approval based on interim results from the PROTECT trial, which demonstrated that sparsentan-treated patients achieved a significantly greater reduction in proteinuria from baseline versus the active control irbesartan and that sparsentan was generally safe and well tolerated. Sparsentan is the first non-immunosuppressive treatment to be FDA-approved for the reduction of proteinuria in adults with IgAN at high risk of disease progression. We provide practical guidance for the clinical use of sparsentan in adults with IgAN.Plain Language Summary: Immunoglobulin A nephropathy (IgAN) is a type of kidney disease that most commonly affects young adults. IgAN can get worse over time and lead to kidney failure within 10– 20 years after being diagnosed. People with IgAN who leak protein in their urine (ie, proteinuria) at high levels are likely to lose their kidneys faster. The Kidney Disease Improving Global Outcomes 2021 clinical practice guidelines recommend reducing the amount of protein in the urine and keeping blood pressure in check to help protect the kidneys. Doctors sometimes give medications that can weaken the immune system to patients with IgAN who are at high risk for faster loss of kidney function; however, these drugs can have troublesome side effects. Sparsentan is a new treatment that is taken in one pill each day. It targets two important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function in IgAN. More than 1200 patients have tried sparsentan in clinical trials, and it seems to be safe and well tolerated. It also reduces protein in the urine much better than irbesartan, a blood pressure medicine often used to treat IgAN. For adults with IgAN at high risk of worsening disease, sparsentan is the first medication approved by the US Food and Drug Administration (FDA) that can reduce protein in the urine without hurting the immune system. This article gives practical advice on how to use sparsentan in adults with IgAN, including who should get it, how to start treatment, and how to check if treatment is working for the patient.Keywords: immunoglobulin A nephropathy, sparsentan, treatment, dual endothelin angiotensin receptor antagonist

Keywords

• immunoglobulin a nephropathy
• sparsentan
• treatment
• dual endothelin angiotensin receptor antagonist